Diseases that are transmitted from animals to humans are the most prevalent type of emerging infectious diseases threatening public health. Lyme disease, caused by the bacterium Borrelia burgdorferi, affects more people than any other arthropod-borne disease (carried by insects or ticks) in the US. The number of human cases continues to rise as the geographic range affected by the bacteria expands. Although managing Lyme disease through vaccination appears many years off, identifying environmental factors that promote the growth and spread of the bacterium or the tick vector, Ixodes scapularis, will aid in developing ecological control strategies that can be effective and long-term solutions to reducing Lyme disease incidence. The major goal of this proposal is to unravel the complex interactions between both B. burgdorferi and I. scapularis and their natural environments that have resulted in the recent increase in the geographic range of Lyme disease. We will investigate the temporal and spatial heterogeneity of B. burgdorferi and I. scapularis in a natural ecosystem and assess the biotic, abiotic, and historical factors that have given rise to that heterogeneity. Identifying and quantifying the effects of these interactions will lead to important insights into the biology and ecology of B. burgdorferi and I. scapularis and ultimately to novel targets for ecological control strategies. We will utilize the rapidly developing statistical tools of phylogeography and landscape genetics to analyze a sample of ticks and bacteria that were collected during the time period that Lyme disease was establishing in the study area. We will use the knowledge gained to develop and experimentally validate predictive models of the spread of Lyme disease into novel environments in the future. In the near term, these studies can lead to a mechanistic understanding of how the environmental factors in a real ecosystem determine the realized geographic range of Lyme disease; few examples are known of a functional basis determining the rate and direction of dispersal of a pathogen and its vector in nature. From a global disease ecology perspective, this work is imperative as the geographic ranges of many infectious diseases are rapidly increasing and encroaching into human communities. These studies will furnish fundamental new insights into factors affecting the geographic spread of, and disease risk from, animal-transmitted pathogens. Our long-term goal is to determine the mechanisms contributing to human Lyme disease risk that could be targeted by ecological control strategies.